2014
Akeju, Oluwaseun; Loggia, Marco L; Catana, Ciprian; Pavone, Kara J; Vazquez, Rafael; Rhee, James; Ramirez, Violeta Contreras; Chonde, Daniel B; Izquierdo-Garcia, David; Arabasz, Grae; Hsu, Shirley; Habeeb, Kathleen; Hooker, Jacob M; Napadow, Vitaly; Brown, Emery N; Purdon, Patrick L
Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness Journal Article
In: Elife, vol. 3, pp. e04499, 2014, ISSN: 2050-084X.
@article{pmid25432022,
title = {Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness},
author = {Oluwaseun Akeju and Marco L Loggia and Ciprian Catana and Kara J Pavone and Rafael Vazquez and James Rhee and Violeta Contreras Ramirez and Daniel B Chonde and David Izquierdo-Garcia and Grae Arabasz and Shirley Hsu and Kathleen Habeeb and Jacob M Hooker and Vitaly Napadow and Emery N Brown and Patrick L Purdon},
doi = {10.7554/eLife.04499},
issn = {2050-084X},
year = {2014},
date = {2014-11-01},
journal = {Elife},
volume = {3},
pages = {e04499},
abstract = {Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α₂-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α₂-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.
Dolman, Andrew J; Loggia, Marco L; Edwards, Robert R; Gollub, Randy L; Kong, Jian; Napadow, Vitaly; Wasan, Ajay D
In: Clin J Pain, vol. 30, no. 10, pp. 839–845, 2014, ISSN: 1536-5409.
@article{pmid24135900,
title = {Phenotype matters: the absence of a positive association between cortical thinning and chronic low back pain when controlling for salient clinical variables},
author = {Andrew J Dolman and Marco L Loggia and Robert R Edwards and Randy L Gollub and Jian Kong and Vitaly Napadow and Ajay D Wasan},
doi = {10.1097/AJP.0000000000000043},
issn = {1536-5409},
year = {2014},
date = {2014-10-01},
journal = {Clin J Pain},
volume = {30},
number = {10},
pages = {839--845},
abstract = {AIMS/OBJECTIVES/BACKGROUND: Studies have associated chronic low back pain (cLBP) with grey matter thinning. But these studies have not controlled for important clinical variables (such as a comorbid affective disorder, pain medication, age, or pain phenotype), which may reduce or eliminate these associations.nnMETHODS: We conducted cortical thickness and voxel-based morphometry (VBM) analyses in 14 cLBP patients with a discogenic component to their pain, not taking opioids or benzodiazepines, and not depressed or anxious. They were age and gender matched to 14 pain-free controls (PFCs). An ROI-driven analysis (regions of interest) was conducted, using 18 clusters from a previous arterial spin labeling study demonstrating greater regional cerebral blood flow (rCBF) in these cLBP subjects than the PFCs. Cortical thickness and VBM-based gray matter volume measurements were obtained from a structural MRI scan and group contrasts were calculated.nnRESULTS: Multivariate analysis of variance showed a trend toward cortical thickening in the right paracentral lobule in cLBP subjects (F1,17=3.667, P<0.067), and significant thickening in the right rostral middle frontal gyrus (F1,17=6.880, P<0.014). These clusters were non-significant after including age as a covariate (P<0.891; P<0.279). A whole-brain cortical thickness and VBM analysis also did not identify significant clusters of thinning or thickening. Exploratory analyses identified group differences for correlations between age and cortical thickness of the right rostral middle frontal gyrus (cLBP: R=-0.03, P=0.9; PFCs: R=-0.81, P<0.001), that is, PFCs demonstrated age-related thinning while cLBP patients did not.nnCONCLUSIONS: Our pilot results suggest that controlling for affect, age, and concurrent medications may reduce or eliminate some of the previously reported structural brain alterations in cLBP.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AIMS/OBJECTIVES/BACKGROUND: Studies have associated chronic low back pain (cLBP) with grey matter thinning. But these studies have not controlled for important clinical variables (such as a comorbid affective disorder, pain medication, age, or pain phenotype), which may reduce or eliminate these associations.nnMETHODS: We conducted cortical thickness and voxel-based morphometry (VBM) analyses in 14 cLBP patients with a discogenic component to their pain, not taking opioids or benzodiazepines, and not depressed or anxious. They were age and gender matched to 14 pain-free controls (PFCs). An ROI-driven analysis (regions of interest) was conducted, using 18 clusters from a previous arterial spin labeling study demonstrating greater regional cerebral blood flow (rCBF) in these cLBP subjects than the PFCs. Cortical thickness and VBM-based gray matter volume measurements were obtained from a structural MRI scan and group contrasts were calculated.nnRESULTS: Multivariate analysis of variance showed a trend toward cortical thickening in the right paracentral lobule in cLBP subjects (F1,17=3.667, P<0.067), and significant thickening in the right rostral middle frontal gyrus (F1,17=6.880, P<0.014). These clusters were non-significant after including age as a covariate (P<0.891; P<0.279). A whole-brain cortical thickness and VBM analysis also did not identify significant clusters of thinning or thickening. Exploratory analyses identified group differences for correlations between age and cortical thickness of the right rostral middle frontal gyrus (cLBP: R=-0.03, P=0.9; PFCs: R=-0.81, P<0.001), that is, PFCs demonstrated age-related thinning while cLBP patients did not.nnCONCLUSIONS: Our pilot results suggest that controlling for affect, age, and concurrent medications may reduce or eliminate some of the previously reported structural brain alterations in cLBP.
Loggia, Marco L; Edwards, Robert R; Harris, Richard E; Napadow, Vitaly
Reply: To PMID 24449585 Miscellaneous
2014, ISSN: 2326-5205.
@misc{pmid24515749,
title = {Reply: To PMID 24449585},
author = {Marco L Loggia and Robert R Edwards and Richard E Harris and Vitaly Napadow},
doi = {10.1002/art.38396},
issn = {2326-5205},
year = {2014},
date = {2014-06-01},
journal = {Arthritis Rheumatol},
volume = {66},
number = {6},
pages = {1684--1685},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Napadow, Vitaly; Li, Ang; Loggia, Marco L; Kim, Jieun; Schalock, Peter C; Lerner, Ethan; Tran, Thanh-Nga; Ring, Johannes; Rosen, Bruce R; Kaptchuk, Ted J; Pfab, Florian
The brain circuitry mediating antipruritic effects of acupuncture Journal Article
In: Cereb Cortex, vol. 24, no. 4, pp. 873–882, 2014, ISSN: 1460-2199.
@article{pmid23222890,
title = {The brain circuitry mediating antipruritic effects of acupuncture},
author = {Vitaly Napadow and Ang Li and Marco L Loggia and Jieun Kim and Peter C Schalock and Ethan Lerner and Thanh-Nga Tran and Johannes Ring and Bruce R Rosen and Ted J Kaptchuk and Florian Pfab},
doi = {10.1093/cercor/bhs363},
issn = {1460-2199},
year = {2014},
date = {2014-04-01},
journal = {Cereb Cortex},
volume = {24},
number = {4},
pages = {873--882},
abstract = {Itch is an aversive sensory experience and while systemic therapies, such as acupuncture, have shown promise in alleviating itch in patients suffering from chronic itch, their antipruritic mechanisms are unknown. As several lines of evidence implicate brain-focused mechanisms, we applied functional magnetic resonance imaging and our validated temperature-modulation itch model to evaluate the underlying brain circuitry supporting allergen-induced itch reduction in atopic dermatitis patients by acupuncture, antihistamine, and respective placebo treatments. Brain response to allergen itch demonstrated phase dependency. During an increasing itch phase, activation was localized in anterior insula and striatum, regions associated with salience/interoception and motivation processing. Once itch reached peak plateau, robust activation was noted in prefrontal cognitive and premotor areas. Acupuncture reduced itch and itch-evoked activation in the insula, putamen, and premotor and prefrontal cortical areas. Neither itch sensation nor itch-evoked brain response was altered following antihistamine or placebo acupuncture. Greater itch reduction following acupuncture was associated with greater reduction in putamen response, a region implicated in motivation and habitual behavior underlying the urge to scratch, specifically implicating this region in acupuncture's antipruritic effects. Understanding brain circuitry underlying itch reduction following acupuncture and related neuromodulatory therapies will significantly impact the development and applicability of novel therapies to reduce an itch.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Itch is an aversive sensory experience and while systemic therapies, such as acupuncture, have shown promise in alleviating itch in patients suffering from chronic itch, their antipruritic mechanisms are unknown. As several lines of evidence implicate brain-focused mechanisms, we applied functional magnetic resonance imaging and our validated temperature-modulation itch model to evaluate the underlying brain circuitry supporting allergen-induced itch reduction in atopic dermatitis patients by acupuncture, antihistamine, and respective placebo treatments. Brain response to allergen itch demonstrated phase dependency. During an increasing itch phase, activation was localized in anterior insula and striatum, regions associated with salience/interoception and motivation processing. Once itch reached peak plateau, robust activation was noted in prefrontal cognitive and premotor areas. Acupuncture reduced itch and itch-evoked activation in the insula, putamen, and premotor and prefrontal cortical areas. Neither itch sensation nor itch-evoked brain response was altered following antihistamine or placebo acupuncture. Greater itch reduction following acupuncture was associated with greater reduction in putamen response, a region implicated in motivation and habitual behavior underlying the urge to scratch, specifically implicating this region in acupuncture's antipruritic effects. Understanding brain circuitry underlying itch reduction following acupuncture and related neuromodulatory therapies will significantly impact the development and applicability of novel therapies to reduce an itch.
Coombs, Garth; Loggia, Marco L; Greve, Douglas N; Holt, Daphne J
Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect Journal Article
In: PLoS One, vol. 9, no. 5, pp. e97466, 2014, ISSN: 1932-6203.
@article{pmid24816735,
title = {Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect},
author = {Garth Coombs and Marco L Loggia and Douglas N Greve and Daphne J Holt},
doi = {10.1371/journal.pone.0097466},
issn = {1932-6203},
year = {2014},
date = {2014-01-01},
journal = {PLoS One},
volume = {9},
number = {5},
pages = {e97466},
abstract = {BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.nnMETHODS: Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.nnRESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.nnCONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.nnMETHODS: Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.nnRESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.nnCONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.
Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Gollub, Randy L; Wasan, Ajay D; Harris, Richard E; Edwards, Robert R; Napadow, Vitaly
Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia Journal Article
In: Arthritis Rheumatol, vol. 66, no. 1, pp. 203–212, 2014, ISSN: 2326-5205.
@article{pmid24449585,
title = {Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia},
author = {Marco L Loggia and Chantal Berna and Jieun Kim and Christine M Cahalan and Randy L Gollub and Ajay D Wasan and Richard E Harris and Robert R Edwards and Vitaly Napadow},
doi = {10.1002/art.38191},
issn = {2326-5205},
year = {2014},
date = {2014-01-01},
journal = {Arthritis Rheumatol},
volume = {66},
number = {1},
pages = {203--212},
abstract = {OBJECTIVE: While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief.nnMETHODS: Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation).nnRESULTS: Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished.nnCONCLUSION: FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/γ-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief.nnMETHODS: Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation).nnRESULTS: Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished.nnCONCLUSION: FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/γ-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.
2013
Kong, Jian; Spaeth, Rosa B; Wey, Hsiao-Ying; Cheetham, Alexandra; Cook, Amanda H; Jensen, Karin; Tan, Ying; Liu, Hesheng; Wang, Danhong; Loggia, Marco L; Napadow, Vitaly; Smoller, Jordan W; Wasan, Ajay D; Gollub, Randy L
S1 is associated with chronic low back pain: a functional and structural MRI study Journal Article
In: Mol Pain, vol. 9, pp. 43, 2013, ISSN: 1744-8069.
@article{pmid23965184,
title = {S1 is associated with chronic low back pain: a functional and structural MRI study},
author = {Jian Kong and Rosa B Spaeth and Hsiao-Ying Wey and Alexandra Cheetham and Amanda H Cook and Karin Jensen and Ying Tan and Hesheng Liu and Danhong Wang and Marco L Loggia and Vitaly Napadow and Jordan W Smoller and Ajay D Wasan and Randy L Gollub},
doi = {10.1186/1744-8069-9-43},
issn = {1744-8069},
year = {2013},
date = {2013-08-01},
journal = {Mol Pain},
volume = {9},
pages = {43},
abstract = {A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients.
Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly
Sustained deep-tissue pain alters functional brain connectivity Journal Article
In: Pain, vol. 154, no. 8, pp. 1343–1351, 2013, ISSN: 1872-6623.
@article{pmid23718988,
title = {Sustained deep-tissue pain alters functional brain connectivity},
author = {Jieun Kim and Marco L Loggia and Robert R Edwards and Ajay D Wasan and Randy L Gollub and Vitaly Napadow},
doi = {10.1016/j.pain.2013.04.016},
issn = {1872-6623},
year = {2013},
date = {2013-08-01},
journal = {Pain},
volume = {154},
number = {8},
pages = {1343--1351},
abstract = {Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.
Loggia, Marco L; Kim, Jieun; Gollub, Randy L; Vangel, Mark G; Kirsch, Irving; Kong, Jian; Wasan, Ajay D; Napadow, Vitaly
Default mode network connectivity encodes clinical pain: an arterial spin labeling study Journal Article
In: Pain, vol. 154, no. 1, pp. 24–33, 2013, ISSN: 1872-6623.
@article{pmid23111164,
title = {Default mode network connectivity encodes clinical pain: an arterial spin labeling study},
author = {Marco L Loggia and Jieun Kim and Randy L Gollub and Mark G Vangel and Irving Kirsch and Jian Kong and Ajay D Wasan and Vitaly Napadow},
doi = {10.1016/j.pain.2012.07.029},
issn = {1872-6623},
year = {2013},
date = {2013-01-01},
journal = {Pain},
volume = {154},
number = {1},
pages = {24--33},
abstract = {Neuroimaging studies have suggested the presence of alterations in the anatomo-functional properties of the brain of patients with chronic pain. However, investigation of the brain circuitry supporting the perception of clinical pain presents significant challenges, particularly when using traditional neuroimaging approaches. While potential neuroimaging markers for clinical pain have included resting brain connectivity, these cross-sectional studies have not examined sensitivity to within-subject exacerbation of pain. We used the dual regression probabilistic Independent Component Analysis approach to investigate resting-state connectivity on arterial spin labeling data. Brain connectivity was compared between patients with chronic low back pain (cLBP) and healthy controls, before and after the performance of maneuvers aimed at exacerbating clinical pain levels in the patients. Our analyses identified multiple resting state networks, including the default mode network (DMN). At baseline, patients demonstrated stronger DMN connectivity to the pregenual anterior cingulate cortex (pgACC), left inferior parietal lobule, and right insula (rINS). Patients' baseline clinical pain correlated positively with connectivity strength between the DMN and right insula (DMN-rINS). The performance of calibrated physical maneuvers induced changes in pain, which were paralleled by changes in DMN-rINS connectivity. Maneuvers also disrupted the DMN-pgACC connectivity, which at baseline was anticorrelated with pain. Finally, baseline DMN connectivity predicted maneuver-induced changes in both pain and DMN-rINS connectivity. Our results support the use of arterial spin labeling to evaluate clinical pain, and the use of resting DMN connectivity as a potential neuroimaging biomarker for chronic pain perception.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neuroimaging studies have suggested the presence of alterations in the anatomo-functional properties of the brain of patients with chronic pain. However, investigation of the brain circuitry supporting the perception of clinical pain presents significant challenges, particularly when using traditional neuroimaging approaches. While potential neuroimaging markers for clinical pain have included resting brain connectivity, these cross-sectional studies have not examined sensitivity to within-subject exacerbation of pain. We used the dual regression probabilistic Independent Component Analysis approach to investigate resting-state connectivity on arterial spin labeling data. Brain connectivity was compared between patients with chronic low back pain (cLBP) and healthy controls, before and after the performance of maneuvers aimed at exacerbating clinical pain levels in the patients. Our analyses identified multiple resting state networks, including the default mode network (DMN). At baseline, patients demonstrated stronger DMN connectivity to the pregenual anterior cingulate cortex (pgACC), left inferior parietal lobule, and right insula (rINS). Patients' baseline clinical pain correlated positively with connectivity strength between the DMN and right insula (DMN-rINS). The performance of calibrated physical maneuvers induced changes in pain, which were paralleled by changes in DMN-rINS connectivity. Maneuvers also disrupted the DMN-pgACC connectivity, which at baseline was anticorrelated with pain. Finally, baseline DMN connectivity predicted maneuver-induced changes in both pain and DMN-rINS connectivity. Our results support the use of arterial spin labeling to evaluate clinical pain, and the use of resting DMN connectivity as a potential neuroimaging biomarker for chronic pain perception.
2012
Loggia, Marco L; Edwards, Robert R; Kim, Jieun; Vangel, Mark G; Wasan, Ajay D; Gollub, Randy L; Harris, Richard E; Park, Kyungmo; Napadow, Vitaly
Disentangling linear and nonlinear brain responses to evoked deep tissue pain Journal Article
In: Pain, vol. 153, no. 10, pp. 2140–2151, 2012, ISSN: 1872-6623.
@article{pmid22883925,
title = {Disentangling linear and nonlinear brain responses to evoked deep tissue pain},
author = {Marco L Loggia and Robert R Edwards and Jieun Kim and Mark G Vangel and Ajay D Wasan and Randy L Gollub and Richard E Harris and Kyungmo Park and Vitaly Napadow},
doi = {10.1016/j.pain.2012.07.014},
issn = {1872-6623},
year = {2012},
date = {2012-10-01},
journal = {Pain},
volume = {153},
number = {10},
pages = {2140--2151},
abstract = {Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.
Loggia, Marco L; Napadow, Vitaly
Multi-parameter autonomic-based pain assessment: more is more? Journal Article
In: Pain, vol. 153, no. 9, pp. 1779–1780, 2012, ISSN: 1872-6623.
@article{pmid22633682,
title = {Multi-parameter autonomic-based pain assessment: more is more?},
author = {Marco L Loggia and Vitaly Napadow},
doi = {10.1016/j.pain.2012.05.010},
issn = {1872-6623},
year = {2012},
date = {2012-09-01},
journal = {Pain},
volume = {153},
number = {9},
pages = {1779--1780},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jensen, Karin B; Berna, Chantal; Loggia, Marco L; Wasan, Ajay D; Edwards, Robert R; Gollub, Randy L
The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain Journal Article
In: Neurosci Lett, vol. 520, no. 2, pp. 156–164, 2012, ISSN: 1872-7972.
@article{pmid22445888,
title = {The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain},
author = {Karin B Jensen and Chantal Berna and Marco L Loggia and Ajay D Wasan and Robert R Edwards and Randy L Gollub},
doi = {10.1016/j.neulet.2012.03.010},
issn = {1872-7972},
year = {2012},
date = {2012-06-01},
journal = {Neurosci Lett},
volume = {520},
number = {2},
pages = {156--164},
abstract = {A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased pain-related activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today's experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased pain-related activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today's experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments.
2011
Wasan, Ajay D; Loggia, Marco L; Chen, Li Q; Napadow, Vitaly; Kong, Jian; Gollub, Randy L
Neural correlates of chronic low back pain measured by arterial spin labeling Journal Article
In: Anesthesiology, vol. 115, no. 2, pp. 364–374, 2011, ISSN: 1528-1175.
@article{pmid21720241,
title = {Neural correlates of chronic low back pain measured by arterial spin labeling},
author = {Ajay D Wasan and Marco L Loggia and Li Q Chen and Vitaly Napadow and Jian Kong and Randy L Gollub},
doi = {10.1097/ALN.0b013e318220e880},
issn = {1528-1175},
year = {2011},
date = {2011-08-01},
journal = {Anesthesiology},
volume = {115},
number = {2},
pages = {364--374},
abstract = {BACKGROUND: The varying nature of chronic pain (CP) is difficult to correlate to neural activity using typical functional magnetic resonance imaging methods. Arterial spin labeling is a perfusion-based imaging technique allowing the absolute quantification of regional cerebral blood flow, which is a surrogate measure of neuronal activity.nnMETHODS: Subjects with chronic low back and radicular pain and matched healthy normal subjects, undergoing identical procedures, participated in three sessions: a characterization and training session and two arterial spin labeling sessions. In the first imaging session, CP (if any) was exacerbated using clinical maneuvers; in the second session, noxious heat was applied to the affected leg dermatome, the intensity of which was matched to the pain intensity level of the CP exacerbations for each back pain subject.nnRESULTS: The clinically significant worsening of ongoing CP (≤ 30%, n = 16) was associated with significant regional blood flow increases (6-10 mm/100 g of tissue/min, P less than 0.01) within brain regions known to activate with experimental pain (somatosensory, prefrontal, and insular cortices) and in other structures observed less frequently in experimental pain studies, such as the superior parietal lobule (part of the dorsal attention network). This effect is specific to changes in ongoing CP as it is observed during worsening CP, but it is not observed after thermal pain application, or in matched, pain-free healthy controls.nnCONCLUSIONS: Study findings demonstrate the use of arterial spin labeling to investigate the neural processing of CP, and these findings are a step forward in the quest for objective biomarkers of the chronic pain experience.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The varying nature of chronic pain (CP) is difficult to correlate to neural activity using typical functional magnetic resonance imaging methods. Arterial spin labeling is a perfusion-based imaging technique allowing the absolute quantification of regional cerebral blood flow, which is a surrogate measure of neuronal activity.nnMETHODS: Subjects with chronic low back and radicular pain and matched healthy normal subjects, undergoing identical procedures, participated in three sessions: a characterization and training session and two arterial spin labeling sessions. In the first imaging session, CP (if any) was exacerbated using clinical maneuvers; in the second session, noxious heat was applied to the affected leg dermatome, the intensity of which was matched to the pain intensity level of the CP exacerbations for each back pain subject.nnRESULTS: The clinically significant worsening of ongoing CP (≤ 30%, n = 16) was associated with significant regional blood flow increases (6-10 mm/100 g of tissue/min, P less than 0.01) within brain regions known to activate with experimental pain (somatosensory, prefrontal, and insular cortices) and in other structures observed less frequently in experimental pain studies, such as the superior parietal lobule (part of the dorsal attention network). This effect is specific to changes in ongoing CP as it is observed during worsening CP, but it is not observed after thermal pain application, or in matched, pain-free healthy controls.nnCONCLUSIONS: Study findings demonstrate the use of arterial spin labeling to investigate the neural processing of CP, and these findings are a step forward in the quest for objective biomarkers of the chronic pain experience.
Loggia, Marco L; Juneau, Mylène; Bushnell, Catherine M
Autonomic responses to heat pain: Heart rate, skin conductance, and their relation to verbal ratings and stimulus intensity Journal Article
In: Pain, vol. 152, no. 3, pp. 592–598, 2011, ISSN: 1872-6623.
@article{pmid21215519,
title = {Autonomic responses to heat pain: Heart rate, skin conductance, and their relation to verbal ratings and stimulus intensity},
author = {Marco L Loggia and Mylène Juneau and Catherine M Bushnell},
doi = {10.1016/j.pain.2010.11.032},
issn = {1872-6623},
year = {2011},
date = {2011-03-01},
journal = {Pain},
volume = {152},
number = {3},
pages = {592--598},
abstract = {In human pain experiments, as well as in clinical settings, subjects are often asked to assess pain using scales (eg, numeric rating scales). Although most subjects have little difficulty in using these tools, some lack the necessary basic cognitive or motor skills (eg, paralyzed patients). Thus, the identification of appropriate nonverbal measures of pain has significant clinical relevance. In this study, we assessed heart rate (HR), skin conductance (SC), and verbal ratings in 39 healthy male subjects during the application of twelve 6-s heat stimuli of different intensities on the subjects' left forearm. Both HR and SC increased with more intense painful stimulation. However, HR but not SC, significantly correlated with pain ratings at the group level, suggesting that HR may be a better predictor of between-subject differences in pain than is SC. Conversely, changes in SC better predicted variations in ratings within a given individual, suggesting that it is more sensitive to relative changes in perception. The differences in findings derived from between- and within-subject analyses may result from greater within-subject variability in HR. We conclude that at least for male subjects, HR provides a better predictor of pain perception than SC, but that data should be averaged over several stimulus presentations to achieve consistent results. Nevertheless, variability among studies, and the indication that gender of both the subject and experimenter could influence autonomic results, lead us to advise caution in using autonomic or any other surrogate measures to infer pain in individuals who cannot adequately report their perception. Skin conductance is more sensitive to detect within-subject perceptual changes, but heart rate appears to better predict pain ratings at the group level.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In human pain experiments, as well as in clinical settings, subjects are often asked to assess pain using scales (eg, numeric rating scales). Although most subjects have little difficulty in using these tools, some lack the necessary basic cognitive or motor skills (eg, paralyzed patients). Thus, the identification of appropriate nonverbal measures of pain has significant clinical relevance. In this study, we assessed heart rate (HR), skin conductance (SC), and verbal ratings in 39 healthy male subjects during the application of twelve 6-s heat stimuli of different intensities on the subjects' left forearm. Both HR and SC increased with more intense painful stimulation. However, HR but not SC, significantly correlated with pain ratings at the group level, suggesting that HR may be a better predictor of between-subject differences in pain than is SC. Conversely, changes in SC better predicted variations in ratings within a given individual, suggesting that it is more sensitive to relative changes in perception. The differences in findings derived from between- and within-subject analyses may result from greater within-subject variability in HR. We conclude that at least for male subjects, HR provides a better predictor of pain perception than SC, but that data should be averaged over several stimulus presentations to achieve consistent results. Nevertheless, variability among studies, and the indication that gender of both the subject and experimenter could influence autonomic results, lead us to advise caution in using autonomic or any other surrogate measures to infer pain in individuals who cannot adequately report their perception. Skin conductance is more sensitive to detect within-subject perceptual changes, but heart rate appears to better predict pain ratings at the group level.
Loggia, Marco L; Jensen, Karin; Gollub, Randy L; Wasan, Ajay D; Edwards, Robert R; Kong, Jian
The catechol-O-methyltransferase (COMT) val158met polymorphism affects brain responses to repeated painful stimuli Journal Article
In: PLoS One, vol. 6, no. 11, pp. e27764, 2011, ISSN: 1932-6203.
@article{pmid22132136,
title = {The catechol-O-methyltransferase (COMT) val158met polymorphism affects brain responses to repeated painful stimuli},
author = {Marco L Loggia and Karin Jensen and Randy L Gollub and Ajay D Wasan and Robert R Edwards and Jian Kong},
doi = {10.1371/journal.pone.0027764},
issn = {1932-6203},
year = {2011},
date = {2011-01-01},
journal = {PLoS One},
volume = {6},
number = {11},
pages = {e27764},
abstract = {Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation.
2010
Campbell, Claudia M; Witmer, Kenny; Simango, Mpepera; Carteret, Alene; Loggia, Marco L; Campbell, James N; Haythornthwaite, Jennifer A; Edwards, Robert R
Catastrophizing delays the analgesic effect of distraction Journal Article
In: Pain, vol. 149, no. 2, pp. 202–207, 2010, ISSN: 1872-6623.
@article{pmid20188470,
title = {Catastrophizing delays the analgesic effect of distraction},
author = {Claudia M Campbell and Kenny Witmer and Mpepera Simango and Alene Carteret and Marco L Loggia and James N Campbell and Jennifer A Haythornthwaite and Robert R Edwards},
doi = {10.1016/j.pain.2009.11.012},
issn = {1872-6623},
year = {2010},
date = {2010-05-01},
journal = {Pain},
volume = {149},
number = {2},
pages = {202--207},
abstract = {Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain+Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the "Pain Alone" session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain+Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the "Pain Alone" session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time.
Kong, Jian; Loggia, Marco L; Zyloney, Carolyn; Tu, Peichi; LaViolette, Peter; Gollub, Randy L
Exploring the brain in pain: activations, deactivations and their relation Journal Article
In: Pain, vol. 148, no. 2, pp. 257–267, 2010, ISSN: 1872-6623.
@article{pmid20005043,
title = {Exploring the brain in pain: activations, deactivations and their relation},
author = {Jian Kong and Marco L Loggia and Carolyn Zyloney and Peichi Tu and Peter LaViolette and Randy L Gollub},
doi = {10.1016/j.pain.2009.11.008},
issn = {1872-6623},
year = {2010},
date = {2010-02-01},
journal = {Pain},
volume = {148},
number = {2},
pages = {257--267},
abstract = {The majority of neuroimaging studies on pain focuses on the study of BOLD activations, and more rarely on deactivations. In this study, in a relatively large cohort of subjects (N=61), we assess (a) the extent of brain activation and deactivation during the application of two different heat pain levels (HIGH and LOW) and (b) the relations between these two directions of fMRI signal change. Furthermore, in a subset of our subjects (N=12), we assess (c) the functional connectivity of pain-activated or -deactivated regions during resting states. As previously observed, we find that pain stimuli induce intensity dependent (HIGH pain>LOW pain) fMRI signal increases across the pain matrix. Simultaneously, the noxious stimuli induce activity decreases in several brain regions, including some of the 'core structures' of the default network (DMN). In contrast to what we observe with the signal increases, the extent of deactivations is greater for LOW than HIGH pain stimuli. The functional dissociation between activated and deactivated networks is further supported by correlational and functional connectivity analyses. Our results illustrate the absence of a linear relationship between pain activations and deactivations, and therefore suggest that these brain signal changes underlie different aspects of the pain experience.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The majority of neuroimaging studies on pain focuses on the study of BOLD activations, and more rarely on deactivations. In this study, in a relatively large cohort of subjects (N=61), we assess (a) the extent of brain activation and deactivation during the application of two different heat pain levels (HIGH and LOW) and (b) the relations between these two directions of fMRI signal change. Furthermore, in a subset of our subjects (N=12), we assess (c) the functional connectivity of pain-activated or -deactivated regions during resting states. As previously observed, we find that pain stimuli induce intensity dependent (HIGH pain>LOW pain) fMRI signal increases across the pain matrix. Simultaneously, the noxious stimuli induce activity decreases in several brain regions, including some of the 'core structures' of the default network (DMN). In contrast to what we observe with the signal increases, the extent of deactivations is greater for LOW than HIGH pain stimuli. The functional dissociation between activated and deactivated networks is further supported by correlational and functional connectivity analyses. Our results illustrate the absence of a linear relationship between pain activations and deactivations, and therefore suggest that these brain signal changes underlie different aspects of the pain experience.
2009
Loggia, Marco L; Bushnell, M Catherine; Tétreault, Martine; Thiffault, Isabelle; Bhérer, Claude; Mohammed, Nazma K; Kuchinad, Anil A; Laferrière, Audrey; Dicaire, Marie-Josée; Loisel, Lina; Mogil, Jeffrey S; Brais, Bernard
Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli Journal Article
In: J Neurosci, vol. 29, no. 7, pp. 2162–2166, 2009, ISSN: 1529-2401.
@article{pmid19228968,
title = {Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli},
author = {Marco L Loggia and M Catherine Bushnell and Martine Tétreault and Isabelle Thiffault and Claude Bhérer and Nazma K Mohammed and Anil A Kuchinad and Audrey Laferrière and Marie-Josée Dicaire and Lina Loisel and Jeffrey S Mogil and Bernard Brais},
doi = {10.1523/JNEUROSCI.4633-08.2009},
issn = {1529-2401},
year = {2009},
date = {2009-02-01},
journal = {J Neurosci},
volume = {29},
number = {7},
pages = {2162--2166},
abstract = {Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in the HSN2 gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p<0.001) and cool (p<0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p=0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p<0.01) and cold pain stimuli (p<0.05), and tend to be more sensitive to cool stimuli (p=0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r=0.76, p=0.02), and in carriers cool detection thresholds did not increase with age (r=0.27, p=0.24) as expected and observed in controls (r=0.34, p=0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in the HSN2 gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p<0.001) and cool (p<0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p=0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p<0.01) and cold pain stimuli (p<0.05), and tend to be more sensitive to cool stimuli (p=0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r=0.76, p=0.02), and in carriers cool detection thresholds did not increase with age (r=0.27, p=0.24) as expected and observed in controls (r=0.34, p=0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.
2008
Loggia, Marco L; Schweinhardt, Petra; Villemure, Chantal; Bushnell, M Catherine
Effects of psychological state on pain perception in the dental environment Journal Article
In: J Can Dent Assoc, vol. 74, no. 7, pp. 651–656, 2008, ISSN: 1488-2159.
@article{pmid18789200,
title = {Effects of psychological state on pain perception in the dental environment},
author = {Marco L Loggia and Petra Schweinhardt and Chantal Villemure and M Catherine Bushnell},
issn = {1488-2159},
year = {2008},
date = {2008-09-01},
journal = {J Can Dent Assoc},
volume = {74},
number = {7},
pages = {651--656},
abstract = {Psychological factors have an important influence on pain perception. Both in the clinic and in experimental settings, distraction has been shown to reduce pain. Further, negative emotions increase pain, whereas positive emotions have the opposite effect. Other more complex psychological states alter the way we feel pain. For instance, empathy for another person who is suffering increases our own pain experience, and expectation of pain relief underlies much of the placebo effect. Neuroimaging studies show a physiological basis for psychological pain modulation, with activity in pain pathways altered by attentional state, positive and negative emotions, empathy and the administration of a placebo. The same psychological factors activate intrinsic modulatory systems in the brain, including those stimulated when opiates are given for pain relief. It is important for the dentist and patients to understand the influence of psychological state on pain transmission. Such an understanding will not only help patients learn how to participate in their own pain control, but will also help the clinician create a fostering environment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Psychological factors have an important influence on pain perception. Both in the clinic and in experimental settings, distraction has been shown to reduce pain. Further, negative emotions increase pain, whereas positive emotions have the opposite effect. Other more complex psychological states alter the way we feel pain. For instance, empathy for another person who is suffering increases our own pain experience, and expectation of pain relief underlies much of the placebo effect. Neuroimaging studies show a physiological basis for psychological pain modulation, with activity in pain pathways altered by attentional state, positive and negative emotions, empathy and the administration of a placebo. The same psychological factors activate intrinsic modulatory systems in the brain, including those stimulated when opiates are given for pain relief. It is important for the dentist and patients to understand the influence of psychological state on pain transmission. Such an understanding will not only help patients learn how to participate in their own pain control, but will also help the clinician create a fostering environment.
Loggia, Marco L; Mogil, Jeffrey S; Bushnell, M Catherine
Experimentally induced mood changes preferentially affect pain unpleasantness Journal Article
In: J Pain, vol. 9, no. 9, pp. 784–791, 2008, ISSN: 1528-8447.
@article{pmid18538637,
title = {Experimentally induced mood changes preferentially affect pain unpleasantness},
author = {Marco L Loggia and Jeffrey S Mogil and M Catherine Bushnell},
doi = {10.1016/j.jpain.2008.03.014},
issn = {1528-8447},
year = {2008},
date = {2008-09-01},
journal = {J Pain},
volume = {9},
number = {9},
pages = {784--791},
abstract = {Our group previously demonstrated that changes in mood induced by pleasant or unpleasant odors affect the perceived unpleasantness of painful heat stimuli, without significantly altering perceived pain intensity. In the present study, we examined whether changing mood by viewing emotionally laden visual stimuli also preferentially alters pain unpleasantness. Twelve female subjects immersed their right hand in hot water while observing a video showing a person experiencing the same type of pain (ie, model condition), unpleasant scenes not involving people (ie, disasters condition), or a cityscape video (ie, cityscape condition). Subjects were asked to rate pain intensity, pain unpleasantness, mood, anxiety/calmness, and video unpleasantness, and their skin conductance was measured throughout the experiment. Pain unpleasantness (but not intensity) ratings were higher during the disasters condition, which was associated with the worst mood, than during the cityscape condition; neither mood nor pain unpleasantness was altered in the model video compared with the cityscape video. Moreover, mood was significantly correlated with pain unpleasantness but not with pain intensity. Because these results are similar to those observed when odors were used to alter mood, we conclude that the effects of mood on the affective components of pain are independent of mood induction technique used.nnPERSPECTIVE: This article provides new evidence that changes in mood affect the pain experience by preferentially modulating pain unpleasantness. This finding could potentially help health professionals to treat pain symptoms in patients with altered mood, suggesting methods of pain management aimed at easing the affective, along with the sensory, components of pain.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Our group previously demonstrated that changes in mood induced by pleasant or unpleasant odors affect the perceived unpleasantness of painful heat stimuli, without significantly altering perceived pain intensity. In the present study, we examined whether changing mood by viewing emotionally laden visual stimuli also preferentially alters pain unpleasantness. Twelve female subjects immersed their right hand in hot water while observing a video showing a person experiencing the same type of pain (ie, model condition), unpleasant scenes not involving people (ie, disasters condition), or a cityscape video (ie, cityscape condition). Subjects were asked to rate pain intensity, pain unpleasantness, mood, anxiety/calmness, and video unpleasantness, and their skin conductance was measured throughout the experiment. Pain unpleasantness (but not intensity) ratings were higher during the disasters condition, which was associated with the worst mood, than during the cityscape condition; neither mood nor pain unpleasantness was altered in the model video compared with the cityscape video. Moreover, mood was significantly correlated with pain unpleasantness but not with pain intensity. Because these results are similar to those observed when odors were used to alter mood, we conclude that the effects of mood on the affective components of pain are independent of mood induction technique used.nnPERSPECTIVE: This article provides new evidence that changes in mood affect the pain experience by preferentially modulating pain unpleasantness. This finding could potentially help health professionals to treat pain symptoms in patients with altered mood, suggesting methods of pain management aimed at easing the affective, along with the sensory, components of pain.
Loggia, Marco L; Mogil, Jeffrey S; Bushnell, M Catherine
Empathy hurts: compassion for another increases both sensory and affective components of pain perception Journal Article
In: Pain, vol. 136, no. 1-2, pp. 168–176, 2008, ISSN: 1872-6623.
@article{pmid17822850,
title = {Empathy hurts: compassion for another increases both sensory and affective components of pain perception},
author = {Marco L Loggia and Jeffrey S Mogil and M Catherine Bushnell},
doi = {10.1016/j.pain.2007.07.017},
issn = {1872-6623},
year = {2008},
date = {2008-05-01},
journal = {Pain},
volume = {136},
number = {1-2},
pages = {168--176},
abstract = {Recent studies demonstrate that some brain structures activated by pain are also engaged when an individual observes someone else in pain, and that these empathy-related responses are modulated as a function of the affective link between the empath and the individual in pain. In this study we test the hypothesis that empathy-evoked activation in the pain network leads to heightened pain perception. After inducing in half of our subjects a state of high empathy for an actor and in the other half a state of low empathy towards him, we measured the sensitivity to heat stimuli of various intensities in healthy participants while they watched the actor being exposed to similar stimuli. Participants in the "high-empathy" group rated painful (but not non-painful) stimuli applied to themselves as more intense and unpleasant than did those in the "low-empathy" group. Positive correlations between state empathy scores and pain ratings further suggest that this perceptual phenomenon depends on the magnitude of empathic response induced in the participants. The effects were observed when subjects watched the model receiving either neutral or painful stimuli, suggesting that it is empathy itself that alters pain perception, and not necessarily the observation of pain behaviors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent studies demonstrate that some brain structures activated by pain are also engaged when an individual observes someone else in pain, and that these empathy-related responses are modulated as a function of the affective link between the empath and the individual in pain. In this study we test the hypothesis that empathy-evoked activation in the pain network leads to heightened pain perception. After inducing in half of our subjects a state of high empathy for an actor and in the other half a state of low empathy towards him, we measured the sensitivity to heat stimuli of various intensities in healthy participants while they watched the actor being exposed to similar stimuli. Participants in the "high-empathy" group rated painful (but not non-painful) stimuli applied to themselves as more intense and unpleasant than did those in the "low-empathy" group. Positive correlations between state empathy scores and pain ratings further suggest that this perceptual phenomenon depends on the magnitude of empathic response induced in the participants. The effects were observed when subjects watched the model receiving either neutral or painful stimuli, suggesting that it is empathy itself that alters pain perception, and not necessarily the observation of pain behaviors.